Booster vaccination with Ad26.COV2.S or an Omicron-adapted vaccine in pre-immune hamsters protects against Omicron BA.2

Maarten Swart, Joan van der Lubbe, Sonja Schmit-Tillemans, Ella van Huizen, Johan Verspuij, Ana Izquierdo Gil, Ying Choi, Chenandly Daal, Aditya Perkasa, Adriaan de Wilde, Erwin Claassen, Rineke de Jong, Katrin E. Wiese, Lisette Cornelissen, Marieke van Es, Marjolein van Heerden, Eleni Kourkouta, Issam Tahiri, Michel Mulders, Jessica VreugdenhilKarin Feddes - de Boer, Leacky Muchene, Jeroen Tolboom, Liesbeth Dekking, Jarek Juraszek, Jort Vellinga, Jerome Custers, Rinke Bos, Hanneke Schuitemaker, Frank Wegmann, Ramon Roozendaal, Harmjan Kuipers, Roland Zahn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)


Since the original outbreak of the SARS-CoV-2 virus, several rapidly spreading SARS-CoV-2 variants of concern (VOC) have emerged. Here, we show that a single dose of Ad26.COV2.S (based on the Wuhan-Hu-1 spike variant) protects against the Gamma and Delta variants in naive hamsters, supporting the observed maintained vaccine efficacy in humans against these VOC. Adapted spike-based booster vaccines targeting Omicron variants have now been authorized in the absence of human efficacy data. We evaluated the immunogenicity and efficacy of Ad26.COV2.S.529 (encoding a stabilized Omicron BA.1 spike) in naive mice and in hamsters with pre-existing immunity to the Wuhan-Hu-1 spike. In naive mice, Ad26.COV2.S.529 elicited higher neutralizing antibody titers against SARS-CoV-2 Omicron BA.1 and BA.2, compared with Ad26.COV2.S. However, neutralizing titers against the SARS-CoV-2 B.1 (D614G) and Delta variants were lower after primary vaccination with Ad26.COV2.S.529 compared with Ad26.COV2.S. In contrast, we found comparable Omicron BA.1 and BA.2 neutralizing titers in hamsters with pre-existing Wuhan-Hu-1 spike immunity after vaccination with Ad26.COV2.S, Ad26.COV2.S.529 or a combination of the two vaccines. Moreover, all three vaccine modalities induced equivalent protection against Omicron BA.2 challenge in these animals. Overall, our data suggest that an Omicron BA.1-based booster in rodents does not improve immunogenicity and efficacy against Omicron BA.2 over an Ad26.COV2.S booster in a setting of pre-existing immunity to SARS-CoV-2.

Original languageEnglish
Article number40
Number of pages12
Journalnpj Vaccines
Publication statusPublished - 16 Mar 2023


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